Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Dysphagia Severity and Quality of Life in Nasopharyngeal Cancer Patients after Intensity Modulated Radiotherapy (IMRT).

Background: Patients treated with definitive radiotherapy for nasopharyngeal carcinoma (NPC) develop severe dysphagia, affecting their quality of life. Traditional prognosis biomarkers are insufficient, leading to a search for new predictors like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Methods: We retrospectively enrolled 44 NPC patients who underwent definitive radiotherapy between 2010 and 2018. EQUATOR and STROBE network guidelines were adopted. Pre-treatment evaluations were conducted, and post-treatment oropharyngeal dysphagia was assessed using the Sydney Swallow Questionnaire (SSQ) and FEES, then assigning a Dysphagia Outcome and Severity Scale (DOSS) level. Patients were divided based on NLR and PLR cut-offs, comparing subjective dysphagia (SSQ) scores and DOSS results at baseline and after a 5-year follow-up. Multiple linear regression was used for analysis. Results: At baseline, the mean NLR was 2.52 ± 1.10, and the PLR was 208.40 ± 94.35. Multivariate analysis indicated NLR and PLR as significant predictors of DOSS outcomes (p < 0.001). Conclusions: Baseline inflammation markers, such as NLR and PLR, may be used to predict dysphagia severity in NPC patients undergoing definitive radiotherapy. These markers could help identify patients at higher risk for severe dysphagia and implement tailored therapeutic and rehabilitative strategies to improve their quality of life. Further studies with larger cohorts are needed to confirm these findings and explore additional prognostic factors for dysphagia outcomes in NPC patients.

Impact of Obstructive Sleep Apnea and Sympathetic Nervous System on Cardiac Health: A Comprehensive Review.

A prevalent condition linked to an elevated risk of cardiovascular disease is sleep apnea. This review examines the connections between cardiac risk, the sympathetic nervous system, and sleep apnea. The increased risk of hypertension, arrhythmias, myocardial infarction, and heart failure was highlighted in the pathophysiology of sleep apnea and its effect on sympathetic activation. It is also important to consider potential processes such as oxidative stress, inflammation, endothelial dysfunction, and autonomic imbalance that may relate sleep apnea-induced sympathetic activation to cardiac risk. With implications for creating innovative diagnostic and treatment approaches to lessen the cardiovascular effects of sleep apnea, the goal of this investigation is to improve the understanding of the intricate link between sympathetic activity, cardiac risk, and sleep apnea. This study aimed to clarify the complex relationship between cardiovascular health and sleep apnea by synthesizing the available research and highlighting the crucial role played by the sympathetic nervous system in moderating this relationship. Our thorough investigation may have important therapeutic ramifications that will direct the creation of focused therapies to enhance cardiovascular outcomes in sleep apnea sufferers.

Oral Health Implications of Obstructive Sleep Apnea: A Literature Review.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep. While the systemic implications of OSA are well documented, the dental consequences are less frequently discussed yet equally significant. This review aims to elucidate the oral health impacts of OSA, emphasizing the importance of interdisciplinary care. METHODS: A comprehensive literature search was conducted across several databases to identify studies examining the relationship between OSA and various oral health parameters. The review included observational studies, clinical trials, and systematic reviews published in English up to January 2024. RESULTS: OSA was significantly associated with heightened risks of bruxism, dry mouth, periodontal disease, temporomandibular joint disorders, palatal and dental changes, and alterations in taste sensation. Mouth breathing associated with OSA was a critical factor in exacerbating xerostomia and dental caries. Furthermore, the systemic inflammation induced by OSA appeared to correlate with the severity of periodontal disease. Patients using oral appliance therapy for OSA also showed notable changes in dental occlusion and required ongoing dental monitoring. CONCLUSIONS: The findings underscore the bidirectional relationship between OSA and oral health, highlighting the need for dental professionals to be integral participants in the management of OSA. Early dental evaluation and intervention can contribute to the overall health and quality of life of individuals with OSA. The review advocates for the development of clinical guidelines to facilitate the early identification and management of OSA-related oral health issues within dental practice and encourages a collaborative approach to patient care.

Concordance in bacterial colonization profiles between voice prostheses and oral microbiota post-laryngectomy: An experimental study.

OBJECTIVE: Knowledge about voice prosthesis microbial colonization is vital in laryngectomized patients' quality of life (QoL). Herein, we aimed to explore the relationship between oral microbial patterns, demographic variables and voice prosthesis performance. METHODS: Thirty laryngectomy patients were assessed for microbial colonization in their voice prostheses and oral cavities. Factors like age, proton pump inhibitor (PPI) usage, and alcohol consumption were considered. RESULTS: Participants' average age was 74.20 ± 7.31 years, with a majority on PPIs. Staphylococcus aureus was the most common bacterium in prostheses (53 %), followed by Pseudomonas aeruginosa (27 %). Candida albicans was the primary fungal colonizer (67 %). A statistically significant moderate correlation was found between fungal species before and after oral rinsing (p = 0.035, Phi=0.588, Cramer's V = 0.416). Voice prosthesis and oral cavity microbiota profiles showed significant concordance (kappa=0.315, p < 0.004). Among subgroup analyses, bacterial patterns of colonization did not significantly influence VHI (p = 0.9555), VrQoL (p = 0.6610), or SF-36 (p = 0.509) scores. Conversely, fungal patterns of VP colonization significantly impacted subjective voice scores, with Candida krusei demonstrating better VHI (35.25 ± 3.63 vs. 44.54 ± 6.33; p = 0.008), VrQoL (7.13 ± 1.69 vs. 10.73 ± 2.00; p = 0.001), and SF-36 (69.36 ± 7.09 vs. 76.50 ± 7.73; p = 0.051) scores compared to C. albicans. CONCLUSIONS: There was a significant correlation between the oral microbiota and voice prosthesis colonization. These insights can inform improved care strategies for voice prostheses, enhancing patient outcomes.

Behçet's Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review.

Behçet's disease is a systemic inflammatory disorder of unknown etiology. The disease manifests with diverse clinical symptoms, most commonly recurrent oral and genital ulcers, skin lesions, and uveitis, though it can affect multiple organ systems. Diagnosis is primarily clinical due to the lack of a definitive diagnostic test, and management involves a multidisciplinary approach to control inflammation and manage symptoms. Current treatment strategies involve corticosteroids, immunosuppressive agents, and, increasingly, biological therapies. Behçet's disease exhibits a higher prevalence along the Silk Road, suggesting a role of environmental and genetic factors. Despite significant progress in understanding its clinical characteristics and treatment approaches, gaps remain in our understanding of its pathogenesis. Future research is needed to elucidate the disease's pathophysiology and optimize treatment strategies.

Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS), affecting approximately 1 billion adults globally, is characterized by recurrent airway obstruction during sleep, leading to oxygen desaturation, elevated carbon dioxide levels, and disrupted sleep architecture. OSAS significantly impacts quality of life and is associated with increased morbidity and mortality, particularly in the cardiovascular and cognitive domains. The cyclic pattern of intermittent hypoxia in OSAS triggers oxidative stress, contributing to cellular damage. This review explores the intricate relationship between OSAS and oxidative stress, shedding light on molecular mechanisms and potential therapeutic interventions. METHODS: A comprehensive review spanning from 2000 to 2023 was conducted using the PubMed, Cochrane, and EMBASE databases. Inclusion criteria encompassed English articles focusing on adults or animals and reporting values for oxidative stress and inflammation biomarkers. RESULTS: The review delineates the imbalance between pro-inflammatory and anti-inflammatory factors in OSAS, leading to heightened oxidative stress. Reactive oxygen species biomarkers, nitric oxide, inflammatory cytokines, endothelial dysfunction, and antioxidant defense mechanisms are explored in the context of OSAS. OSAS-related complications include cardiovascular disorders, neurological impairments, metabolic dysfunction, and a potential link to cancer. This review emphasizes the potential of antioxidant therapy as a complementary treatment strategy. CONCLUSIONS: Understanding the molecular intricacies of oxidative stress in OSAS is crucial for developing targeted therapeutic interventions. The comprehensive analysis of biomarkers provides insights into the complex interplay between OSAS and systemic complications, offering avenues for future research and therapeutic advancements in this multifaceted sleep disorder.

Pediatric Lemierre's Syndrome: A Comprehensive Literature Review.

BACKGROUND: Lemierre syndrome is a rare, potentially fatal complication of oropharyngeal infections characterized by septic thrombophlebitis of the internal jugular vein. It primarily affects healthy adolescents and young adults. Its incidence declined after the antibiotic era, but it may have resurged in recent decades, likely due to judicious antibiotic use and increasing bacterial resistance. Prompt diagnosis and treatment are imperative to prevent significant morbidity and mortality. METHODS: Lemierre syndrome has been called "the forgotten disease," with a reported incidence of around 3.6 cases per million. The mean age at presentation is around 20 years old, though it can occur at any age. Lemierre Syndrome follows an oropharyngeal infection, most commonly pharyngitis, leading to septic thrombophlebitis of the internal jugular vein. F. necrophorum is the classic pathogen, though other organisms are being increasingly isolated. Metastatic infections, especially pulmonary, are common complications. Contrast-enhanced CT of the neck confirming internal jugular vein thrombosis is the gold standard for diagnosis. Long-course broad-spectrum IV antibiotics covering anaerobes are the mainstays of the disease's treatment. Anticoagulation may also be considered. Mortality rates are high without treatment, but most patients recover fully with appropriate therapy. CONCLUSIONS: Lemierre syndrome should be suspected in patients with prolonged pharyngitis followed by unilateral neck swelling and fevers. Early diagnosis and prompt antibiotic therapy are key, given the potential for disastrous outcomes if untreated. An increased awareness of Lemierre syndrome facilitates its timely management.

The Stearoyl-CoA Desaturase-1 (Desat1) in Drosophila cooperated with Myc to Induce Autophagy and Growth, a Potential New Link to Tumor Survival.

Lipids are an important energy supply in our cells and can be stored or used to produce macromolecules during lipogenesis when cells experience nutrient starvation. Our proteomic analysis reveals that the Drosophila homologue of human Stearoyl-CoA desaturase-1 Desat1) is an indirect target of Myc in fat cells. Stearoyl-CoA desaturases are key enzymes in the synthesis of monounsaturated fatty acids critical for the formation of complex lipids such as triglycerides and phospholipids. Their function is fundamental for cellular physiology, however in tumors, overexpression of SCD-1 and SCD-5 has been found frequently associated with a poor prognosis. Another gene that is often upregulated in tumors is the proto-oncogene c-myc, where its overexpression or increased protein stability, favor cellular growth. Here, we report a potential link between Myc and Desat1 to control autophagy and growth. Using Drosophila, we found that expression of Desat1, in metabolic tissues like the fat body, in the gut and in epithelial cells, is necessary for Myc function to induce autophagy a cell eating mechanism important for energy production. In addition, we observed that reduction of Desat1 affects Myc ability to induce growth in epithelial cells. Our data also identify, in prostatic tumor cells, a significant correlation between the expression of Myc and SCD-1 proteins, suggesting the existence of a potential functional relationship between the activities of these proteins in sustaining tumor progression.

Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of Toll and Eiger/TNF signaling.

High tumor burden is associated with increased levels of circulating inflammatory cytokines that influence the pathophysiology of the tumor and its environment. The cellular and molecular events mediating the organismal response to a growing tumor are poorly understood. Here, we report a bidirectional crosstalk between epithelial tumors and the fat body-a peripheral immune tissue-in Drosophila. Tumors trigger a systemic immune response through activation of Eiger/TNF signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally, Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor cell death. Hemocytes play a critical role in this system by producing the ligands Spätzle and Eiger, which are required for Toll activation in the fat body and tumor cell death. Altogether, our results provide a paradigm for a long-range tumor suppression function of adipocytes in Drosophila, which may represent an evolutionarily conserved mechanism in the organismal response to solid tumors.

Inositol phosphates induce DAPI fluorescence shift.

The polymer inorganic polyP (polyphosphate) and inositol phosphates, such as IP6 (inositol hexakisphosphate; also known as phytic acid), share many biophysical features. These similarities must be attributed to the phosphate groups present in these molecules. Given the ability of polyP to modify the excitation-emission spectra of DAPI we decided to investigate whether inositol phosphates possess the same property. We discovered that DAPI-IP6 complexes emit at approximately 550 nm when excited with light of wavelength 410-420 nm. IP5 (inositol pentakisphosphate) is also able to induce a similar shift in DAPI fluorescence. Conversely, IP3 (inositol trisphosphate) and IP4 (inositol tetrakisphosphate) are unable to shift DAPI fluorescence. We have employed this newly discovered feature of DAPI to study the enzymatic activity of the inositol polyphosphate multikinase and to monitor phytase phosphatase reactions. Finally, we used DAPI-IP6 fluorescence to determine the amount of IP6 in plant seeds. Using an IP6 standard curve this straight-forward analysis revealed that among the samples tested, borlotti beans possess the highest level of IP6 (9.4 mg/g of dry mass), whereas the Indian urad bean the lowest (3.2 mg/g of dry mass). The newly identified fluorescence properties of the DAPI-IP5 and DAPI-IP6 complexes allow the levels and enzymatic conversion of these two important messengers to be rapidly and reliably monitored.

dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1 resulting in organismal growth.

Drosophila dMyc (dMyc) is known for its role in cell-autonomous regulation of growth. Here we address its role in the fat body (FB), a metabolic tissue that functions as a sensor of circulating nutrients to control the release of Drosophila Insulin-like peptides (Dilps) from the brain influencing growth and development. Our results show that expression of dMyc in the FB affects development and animal size. Expression of dMyc, but not of CycD/cdk4 or Rheb, in the FB diminishes the ability to retain Drosophila Insulin-like peptide-2 (DILP2) in the brain during starvation, suggesting that expression of dMyc mimics the signal that remotely controls the release of Dilps into the hemolymph. dMyc also affects glucose metabolism and increases the transcription of Glucose-transporter-1 mRNA, and of Hexokinase and Pyruvate-Kinase mRNAs, key regulators of glycolysis. These animals are able to counteract the increased levels of circulating trehalose induced by a high sugar diet leading to the conclusion that dMyc activity in the FB promotes glucose disposal. dMyc expression induces cell autonomous accumulation of triglycerides, which correlates with increased levels of Fatty Acid Synthase and Acetyl CoA Carboxylase mRNAs, enzymes responsible for lipid synthesis. We also found the expression of Stearoyl-CoA desaturase, Desat1 mRNA significantly higher in FB overexpressing dMyc. Desat1 is an enzyme that is necessary for monosaturation and production of fatty acids, and its reduction affects dMyc's ability to induce fat storage and resistance to animal survival. In conclusion, here we present novel evidences for dMyc function in the Drosophila FB in controlling systemic growth. We discovered that dMyc expression triggers cell autonomous mechanisms that control glucose and lipid metabolism to favor the storage of nutrients (lipids and sugars). In addition, the regulation of Desat1 controls the synthesis of triglycerides in FB and this may affect the humoral signal that controls DILP2 release in the brain.

Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo.

BACKGROUND: Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR) pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways. RESULTS: Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3ß ) a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3ß activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia. CONCLUSIONS: Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At the biochemical level we found that both these pathways converge at GSK3ß to control Myc protein stability, while our genetic analysis shows that insulin and TOR pathways have different requirements for Myc activity during development of the eye, suggesting that Myc might be differentially induced by these pathways during growth or proliferation of cells that make up the ommatidia.

Epithelial delamination and migration: lessons from Drosophila.

Metastasis is the most deadly phase of cancer progression, during which cells detach from their original niche to invade distant tissues, yet the biological processes underlying the spread of cancer are still poorly understood. The fruit fly Drosophila melanogaster provides important insights in our understanding of how epithelial cells migrate from their original location and find their way into surrounding and distant tissues in the metastatic process. Here we review recent studies on the mechanisms of migration of embryonic haemocytes, the macrophage-like immuno-surveillance cells, during normal development and wound healing. We highlight the interesting finding that hydrogen peroxide (H2O2) has been identified as the driving force for haemocyte chemotaxis. We also give a special emphasis to studies suggesting the concept that haemocytes, together with the tumor microenvironment, act as potential inducers of the epithelial de-lamination required for tumor invasion. We propose that cell delamination and migration could be uncoupled from loss of cell polarity via a tumor-related inflammatory response.

Identification of domains responsible for ubiquitin-dependent degradation of dMyc by glycogen synthase kinase 3beta and casein kinase 1 kinases.

In the present study, we report that ubiquitin-mediated degradation of dMyc, the Drosophila homologue of the human c-myc proto-oncogene, is regulated in vitro and in vivo by members of the casein kinase 1 (CK1) family and by glycogen synthase kinase 3beta (GSK3beta). Using Drosophila S2 cells, we demonstrate that CK1alpha promotes dMyc ubiquitination and degradation with a mechanism similar to the one mediated by GSK3beta in vertebrates. Mutation of ck1alpha or -epsilon or sgg/gsk3beta in Drosophila wing imaginal discs results in the accumulation of dMyc protein, suggesting a physiological role for these kinases in vivo. Analysis of the dMyc amino acid sequence reveals the presence of conserved domains containing potential phosphorylation sites for mitogen kinases, GSK3beta, and members of the CK1 family. We demonstrate that mutations of specific residues within these phosphorylation domains regulate dMyc protein stability and confer resistance to degradation by CK1alpha and GSK3beta kinases. Expression of the dMyc mutants in the compound eye of the adult fly results in a visible defect that is attributed to the effect of dMyc on growth, cell death, and inhibition of ommatidial differentiation.